The purpose of this project is to study immune responses in man and experimental animals to natural and experimental rickettsial infections. Serological parameters were compared in 15 cases of Coxiella burnetii infection comprising 5 cases of primary Q fever, chronic granulomatous hepatitis, and endocarditis. The diagnosis was made on the basis of clinical history and serology and on the isolation of C. burnetii phase I organism from biopsy specimens of liver and bone marrow from two patients with granulomatous hepatitis and from the aortic valve vegetations of five patients with endocarditis. The temporal sequences of immunoglobulin levels, rheumatoid factor, and specific antibody responses to phase II and phase I antigens of C. burnetii were evaluated as predictive correlates of the 3 Q fever entities by microagglutination (MA), complement fixation (CF), and indirect immunofluorescence tests (IFA). Serum levels of immunoglobulin classes G, M, and A were variable in all entities of Q fever. Increased mean levels of immunoglobulin G (IgG) and IgA were noted with chronic disease in the sera of some patients, whereas IgM levels were not significantly elevated in chronic disease but not in primary Q fever. The high phase-specific IgA antibody titers in the indirect microimmuno-fluorescence test were diagnostic for endocarditis. This project also evaluates a recently developed serological technique (ELISA) for the diagnosis of bacterial (especially rickettsial) diseases. It also provides serological support to other RML units and includes serodiagnosis of bacterial, rickettsial, or viral diseases under investigation, the monitoring of employees, visiting investigators, and experimental animals for antibodies against various infectious agents.